Large granular lymphocytes are universally increased in human, macaque, and feline lentiviral infection

Large granular lymphocytes (LGLs) have only been anecdotally reported in HIV infection. We previously reported an LGL lymphocytosis in FIV-infected cats associated with a rise in FIV proviral loads and a marked neutropenia that persisted during chronic infection. Extensive immunophenotyping of peripheral blood mononuclear cells in cats chronically infected with FIV were identified LGLs as CD8lo+FAS+; this cell population expanded commensurate with viral load. CD8lo+FAS+ cells expressed similar levels of interferon-γ compared to CD8lo+FAS+ cells from FIV-naive control animals, yet CD3ɛ expression, which was increased on total CD8+ T cells in FIV-infected cats, was decreased on CD8lo+FAS+ cells. Down-modulation of CD3 expression was reversed after culturing PBMC for 3 days in culture with ConA/IL-2. We identified CD8lo+FAS+ LGLs to be polyclonal T cells lacking CD56 expression. Blood smears from HIV-infected individuals and SIVmac239-infected rhesus macaques revealed increased LGLs compared to HIV/SIV negative counterparts. In humans, there was no correlation with viral load or treatment and in macaques the LGLs arose in acute SIV infection with increases in viremia. This is the first report describing and partially characterizing LGL lymphocytosis in association with lentiviral infections in three different species.